Fungal sterol 14α-demethylase (Cytochrome P450 14α-demethylase) (CYP51 (or Erg11p in *Saccharomyces cerevisiae*))

Fungal cytochrome P450 14α-demethylase, commonly referred to as CYP51, is a highly conserved enzyme integral to the biosynthesis of ergosterol, a major structural component of the fungal cell membrane. It catalyzes the demethylation of lanosterol at the 14α position via three oxidative steps, requiring molecular oxygen and NADPH, and is characterized by a heme prosthetic group crucial for its monooxygenase activity. The enzyme is the molecular target for azole antifungals, which inhibit ergosterol synthesis and thereby disrupt membrane integrity, leading to growth inhibition or death of the fungus. CYP51 is encoded by ERG11 in many fungi, and alterations in its gene or structure confer resistance to azole drugs. While CYP51 orthologs exist in animals and plants, the fungal version is especially targeted for antifungal drug development owing to its essential role in fungal viability and pathogenicity.

Other names

Sterol 14α-demethylaseLanosterol 14α-demethylaseCYP51Erg11 (ERG11 gene encodes this enzyme in yeast and some fungi)

Azoles bind to the heme iron of CYP51, blocking the demethylation of lanosterol (ergosterol precursor), thereby inhibiting ergosterol production and causing accumulation of toxic sterol intermediates, leading to fungal cell membrane disruption and death.